Infant cues, such as smiling or crying facial expressions, are powerful motivators of human maternal behavior, activating dopamine-associated brain reward circuits. Oxytocin, a neurohormone of attachment, promotes maternal care in animals, although its role in human maternal behavior is unclear. We examined 30 first-time new mothers to test whether differences in attachment, based on the Adult Attachment Interview, were related to brain reward and peripheral oxytocin response to infant cues. On viewing their own infant’s smiling and crying faces during functional MRI scanning, mothers with secure attachment showed greater activation of brain reward regions, including the ventral striatum, and the oxytocin-associated hypothalamus/pituitary region. Peripheral oxytocin response to infant contact at 7 months was also significantly higher in secure mothers, and was positively correlated with brain activation in both regions. Insecure/dismissing mothers showed greater insular activation in response to their own infant’s sad faces. These results suggest that individual differences in maternal attachment may be linked with development of the dopaminergic and oxytocinergic neuroendocrine systems.